Angiotensin responsiveness in hyperfiltering and nonhyperfiltering diabetic rats

Abstract

Renal and systemic responses to angiotensin II were studied in hyperglycemic diabetic rats (streptozotocin, 60 mg/kg, i.v.) and vehicle-injected controls at 24 h, 1 wk, 2 mo, or at 6 to 12 mo. In normal rats, the GFR was less than 0.80 mL/min per 100 g body wt (0.57 +/- 0.02 mL/min per 100 g body wt; range: 0.40 to 0.79 mL/min per 100 g body wt; N = 45). Hyperfiltration (GFR > or = 0.80 mL/min per 100 g body wt) was observed in all diabetic rats studied at 1 wk (GFR, 1.03 +/- 0.07 mL/min per 100 g body wt; N = 5; P < 0.001 versus control). However, at earlier and later times, GFR was elevated in only 8 of 18 of the diabetic rats (44%), with an overall prevalence of 56% (13 of 23). Mean arterial pressure, plasma glucose, urine volume, and filtration fraction were not different in hyperfiltering diabetic rats compared with nonhyperfiltering diabetic rats or normal controls. Angiotensin II (12.5 ng/kg per minute i.v.) had no effect on GFR in normal rats or nonhyperfiltering diabetic rats, but it normalized GFR in hyperfiltering diabetic rats (0.74 +/- 0.05 mL/min per 100 g body wt). In contrast with the renal effects of angiotensin II, blood pressure responses were similar in hyperfiltering and nonhyperfiltering diabetic rats. The findings that angiotensin II infusion caused a greater fall in GFR in hyperfiltering diabetic rats than in nonhyperfiltering diabetic rats, but that blood pressure responses were similar, suggests a localized abnormality in angiotensin responsiveness in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)